DESCRIPTION, OVERALL (provided by applicant): The University of Southern California Research Center for Liver Diseases, funded since 1995, has the goal of fostering and facilitating interdisciplinary research in liver and digestive disease. The Center has 41 members and 17 affiliated members. The Biomedical Research Base consists of four major Themes supported by 57 peer-reviewed grants totaling $10.8 million in annual direct costs. These Themes include: a) viral hepatitis and liver cancer;b) liver injury;c) cell biology, signal transduction, and transport;d) metabolism and gene expression. Four core facilities support this Research Base: 1) Administrative Core which oversees the operations and budget of the Center;the Center Director, Associate Director, Executive Committee, Administrator and External Advisory Board oversee the utilization of the cores, the pilot/feasibility program, and the enrichment program (seminar series and annual symposium);a Mathematical-Analysis Modeling and Image Processing Subcore is available to Center members through the Administrative Core;2) Molecular Biology Core which is divided into three components: a Central Core which provides access to teaching and equipment as well as specialized techniques, a Proteomic Subcore, and a Microarray Subcore;3) Cell Biology Core which is divided into a Subcellular Organelle Subcore, which provides cell fractionation, specialized preparations (domaine-enriched vesicles, perfused liver), and access to equipment, and a Confocal Microscopy Subcore which provides imaging of live and fixed cells using various platforms including a new ancillary multiphoton confocal microscope;4) Cell Culture Core which provides isolated and primary cultured rat, mouse and human hepatocytes and various cell lines. The Center supports Pilot Feasibility projects in diverse areas related to the Themes of the Research Base. Current projects including a) studies to define the mechanism of entry and exit and intracellular trafficking of adenovirus in hepatocytes;b) the characterization of tight junctional claudins in intestinal epithelia and their role in regulation of paracellular permeability;c) the mechanism of endotoxin-induced stabilization of TNF mRNA: role of methylation of stabilizing protein;d) examination of the structure-function of the intestinal transporter, PepT1. The USC Research Center for Liver Diseases remains dedicated to attracting, promoting, and supporting research aimed at understanding, preventing, and treating liver and digestive diseases.